Genetic link discovered by Clubfoot Specialist at Shriners Hospital for Children

Research Study
Clubfoot Gene Identified
Discovery May Lead to Better Treatments, Therapies

The opportunity to study a family with a multi-generational history of clubfoot has led to the discovery of a gene mutation critical in early limb development called PITX1. Clubfoot affects one in 1,000 live births and is the most common inherited musculoskeletal birth defect. Genetic factors clearly play a role in its cause as 25 percent of all clubfoot cases are familial in nature. Identifying the genes that contribute to clubfoot deformity is the first step toward the development of improved genetic counseling and therapies.

The study began with an infant patient of Matthew Dobbs, M.D., associate professor of orthopedic surgery at Washington University School of Medicine and clubfoot specialist at St. Louis Children’s Hospital and Shriners Hospital for Children—St. Louis. The child is a member of a large family that has been affected by clubfoot over several generations. Dobbs and Christina Gurnett, M.D., Ph.D., assistant professor of neurology, of pediatrics and of orthopedic surgery at the Washington University School of Medicine discovered that of the 35 extended family members analyzed, 13 had lower limb abnormalities, including clubfoot. Further analysis by the research team showed there was a mutation of a gene on the same chromosome in each affected family member.

“This is the first time a gene has been implicated in the development of clubfoot,” said Dr. Dobbs. “Identifying such large families with clubfoot is much easier at Shriners Hospitals than other hospital systems because of the excellent record keeping and the large number of patients in the system. We have a large patient database collected including DNA samples from hundreds of children and their family members with clubfoot. Screening these other clubfoot patients for the same or similar gene mutations is currently underway.”

Dr. Dobbs explained that clubfoot is multi-factorial in origin, meaning that multiple genes and environmental factors are most likely responsible. All of the causes of clubfoot will not be explained by one gene. In order to investigate potential environmental factors, the research team is distributing questionnaires to participating families to gain information on conditions during pregnancy and other historical issues that may factor into the incidence of clubfoot.

“The discovery of this gene’s role in limb development is important because it puts us on the right path toward understanding why clubfoot occurs. Once the causes of clubfoot are better understood we can begin to work on new treatments and potentially preventive strategies for this common and serious musculoskeletal disorder,” Dr. Dobbs said.

The full study, Asymmetric Lower-Limb Malformations in Individuals with Homeobox PITX1 Gene Mutation, was published in the Nov. 17, 2008 issue of American Journal of Human Genetics.

Washington University School of Medicine (2008, October 24). First Gene for Clubfoot Identified. Science Daily. Retrieved December 9, 2008, from http://sciencedaily.com/releases/2008/10/081023144101.htm